SEDATIVES & HYPNOTICS

Presented By: Ms. Kalaivani Sathish M. PharmAssistant Professor,PIMS - PanipatSEDATIVES & HYPNOTICS

SEDATIVE & HYPNOTICSSedative is a drug that produces calming or quietening effect and reduces excitement, it may induce drowsiness.Hypnotics is a drug that induces sleep, resembling natural sleep.

CLASSIFICATIONI. BenzodiazepinesLong Acting 24 48 Hrs (Diazepam, Clonazepam, Chlordiazepoxide)Short Acting 12 24 Hrs (Nitrazepam, Lorazepam and Alprazolam)Ultra Short Acting - < than 6 Hrs (Triazolam, Midazolam)II. Newer agents Zolpidam,Zopiclone

CLASSIFICATION (Cont...)III. Barbiturates Thiopentone, Phenobarbitone, Mephobarbitone, Pentobarbitone.IV. Miscellaneous Paraldehyde, Chloral Hydrate

BENZODIAZEPINEChlordiazepoxide was the first BZD.Pharmacological ActionIt includesSedation and HypnosisReduction in anxietyAnestheticMuscle RelaxationAnti Convulsion effectAmnesia

MECHANISM OF ACTIONGamma-aminobutric acid(GABA) is the principle inhibitory neurotransmitter of the CNS and it acts through GABA receptors.BZD bind to the GABA-A receptor and increase the frequency of chloride channel opening.this inturn leads to increased flow of chloride into the neurons,resulting in hyperpolarization.

In CNS (GABA)

BZD binds with GABA A Receptors

Increase the Frequency of Cl Ions Channel Opening

Increase the Flow of Cl into the neurons

Hyperpolarisation

BZD AS HYPNOTICS WHEN COMPARED TO BARBITURATES1.BZD induce sleep which more resembles natural sleep and has less hangover.2.In hypnotic doses they do not affect respiration or cardiovascular function.3.BZD have safer than barbiturates even in over doses.4.In case overdose a specific BZD antagonist flumazenil can be used to reverse the symptoms.

BZD AS HYPNOTICS WHEN COMPARED TO BARBITURATES5. BZD do not cause microsomsal enzyme induction and therefore do not alter the blood level of other drug.6.BZD have lower abuse liability.

pharmacokinecticsBZD are completely absorbed on oral administration .IM absorption is slow hence oral route is preferred. they are extensively bound to plasm protein metabolized in the liver.

Absorbed well in Orally

Binds with plasma protein

Metabolized in Liver

Excreted by kidney

Adverseeffect Drowsiness, confusion, amnesia, lethargy,weakness, headache, blurred vision, ataxia, day time sedation, while on BZD driving should be avoided.

uses1.Insomnia 2.In anxiety status3.Anticonvulsant4.Muscle relaxant5.As pre anesthetic medication6.During alcohol withdrawal7.General anesthesia8.In psychiatry

BZD ANTAGONIST

FLUMAZENILIt is a BZD receptor antagonist .given IV flumazenil is rapid and short acting.it may rarely induce seizures.USESTo reverse BZD sedation / anesthesia.In BZD overdosage.

neweragentZOLPIDEMIt is a good hypnotic but has weak anticonvulsant.and muscle relaxant effect. It isShort acting but sleep continue for a long time.ESZOPICLONEIt is metabolized by hepatic microsomal enzymes,adverse effects dryness of mouth ,metalic taste.

Neweragent usesThe newer drugs have similar efficacy as BZD in the treatment of insomnia.minimum day after drowsiness and less amnesia.

Barbiturates classificationBarbiturates are derivative of barbituric acid .It can be classified based on the duration of action,1.Long acting-Phenobarbitone,mephobarbotone.2.Short acting Pentobarbitone,butobarbitone.3.Ultra short acting-Thiopentone,hexobarbitone.

Mechanism of actionBarbiturates bind to a specific site on the GABA receptor and facilitate inhibitory neurotransmission by opening chloride ion channels and hyperpolarize the neural membrane.

In CNS (GABA)

BZD binds with GABA A Receptors

Increase the Frequency of Cl Ions Channel Opening

Increase the Flow of Cl into the neurons

Inhibits neurotransmission&Hyperpolarisation

PharmacokinecticsBarbiturates are well absorbed and widely distributed in the body.The highly lipid soluble barbiturates like thiopentone have a fast onset of action .It metabolized in liver.The metabolites are excreted in urine.

Absorbed well in Orally

Binds with plasma protein

Metabolized in Liver

Excreted in urine

Adverse reactionNausea, vomitting,vertigo ,and diarrhea, respiratory depression, skin rashes ,swelling of the eyelids and lips.

Tolerance and dependenceOn repeated administration tolerance develops to the effect of barbiturates developement of both psychological physiologocal dependence to Barbiturates.

Acute barbiturates poisoningThe fatal dose of barbiturates is 6-10grams.Symptoms- respiratory depression,slow and shallow breathing ,hypotension,skin eruption,cardiovascular collapse,and renal failure.

treatmentThere is no specific antidote.1.Gastric lavage followed by administration of activated charcoal to prevent further absorption of barbiturates.2.General supportive measures like maintenance of BP,adequate ventillation and oxygen administration.3.Forced alkaline diuresis.4.Hemodialysis should be done especially if there is renal failure.

miscellaneous

MELATONIN:The hormone secreted by the pineal gland is known to regulate sleep.melatonin act on melatonin recepors.it does not depress the CNS it improves the quality of sleep and helps in withdrawing BZD after long term use.RAMELTEON:It is an agonist at the melatonin receptors is a novel hypnotic drug.it does not modify the sleep .the duration of action is prolonged .adverse effect dizziness and fatigue.

miscellaneous

CHORAL HYDRATEIt is used as an alternative to BZD .It has a bad taste and is an irritant causes nausea and vomitting. It produce hypnosis without affecting respiatory and cardiovasular funtion.PARALDEHYDEIt is a colourless,transperant,pungent,inflammable liquid. It is an irritant and can dissolve plastic cannot be given by aplastic syringe.it also has anticonvulsant properties.

miscellaneous

PARALDEHYDEIt is given rectally ,IM,or orally.USES 1.AS Convulsant in status epilepticus particularly in children.2. Hypnotic rarely used.